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Animal Mitochondrial Genetics02:59

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Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
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The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
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A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
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The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
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A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
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Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
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Mitochondrial Heterogeneity.

Juvid Aryaman1,2,3, Iain G Johnston4,5, Nick S Jones1,5

  • 1Department of Mathematics, Imperial College London, London, United Kingdom.

Frontiers in Genetics
|February 12, 2019
PubMed
Summary
This summary is machine-generated.

Mitochondrial DNA (mtDNA) variations within and between cells drive cellular heterogeneity and impact cell behavior. Understanding this mitochondrial heterogeneity is key to explaining cellular noise and disease.

Keywords:
cellular noisecomplementationheteroplasmy variancemacroheteroplasmymicroheteroplasmymitochondria

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Area of Science:

  • Cellular Biology
  • Mitochondrial Biology
  • Genetics

Background:

  • Cell-to-cell heterogeneity influences critical biological processes like cell fate and drug resistance.
  • Mitochondria, with their multiple DNA copies (mtDNA), are increasingly recognized as key contributors to cellular heterogeneity.
  • Intra-cellular and inter-cellular variations in mtDNA (microheteroplasmy and macroheteroplasmy) can drive cellular noise.

Purpose of the Study:

  • To review the sources of mitochondrial heterogeneity, encompassing genetic and non-genetic factors.
  • To explore the links between mitochondrial genotype and phenotype.
  • To discuss the implications of mitochondrial heterogeneity for cellular processes and future research.

Main Methods:

  • Literature review of genetic and non-genetic sources of mitochondrial heterogeneity.
  • Discussion of mtDNA mutation dynamics (microheteroplasmy and macroheteroplasmy).
  • Analysis of factors influencing mitochondrial genotype-phenotype links, including supercomplexes, cristae, pH, cardiolipin, membrane potential, and networks.

Main Results:

  • Mitochondrial heterogeneity arises from variations within and between cells, influenced by both genetic and non-genetic factors.
  • mtDNA copy number homeostasis and pervasive intra-cellular mutations (microheteroplasmy) are observed.
  • Inter-cellular mtDNA mutations (macroheteroplasmy) and factors like mitochondrial supercomplexes and membrane potential amplify genotype-phenotype links.

Conclusions:

  • Mitochondrial heterogeneity is a significant driver of cellular heterogeneity and cellular noise.
  • Understanding mitochondrial genotype-phenotype relationships is crucial for comprehending cellular diversity.
  • Future research should focus on single-cell mitochondrial measurements to further elucidate these mechanisms.